The primary objective of this research is to continue to develop new strategies for the construction of complex carbocyclic or heterocyclic ring systems. It is expected that this new methodology will expedite the syntheses of biologically active com- pounds and, in addition, provide routes to important previously unsynthesized compounds. These new strategies are based on the further exploitation of a general carbocycle synthesis developed in these laboratories, namely, the ring contraction of macrocyclic lactones to carbo- or hetereocycles via Claisen rearrangement of ketene acetals. The targeted compounds are primarily comprised of medium and/or strained ring systems. For example, the strained in,out- bicyclo(4.4.1) undecan-7-one substructure of the ingenane class of compounds will be constructed by application of this methodology in a proposed synthesis of ingenol. Furthermore, analogs of the tumor promoter ingenol 3-hexadecanoate will be prepared for the purpose of testing and refining pharmacophore hypotheses which develop structural activity relationships for various tumor promoters. A long range goal is to discover tumor promoter analogs which elicit more specific biological responses and tumor promoter antagonists which retain the outstanding binding affinities for the tumor promoter binding site. An exceptionally short, efficient synthesis of the taxane ring system which exploits the Claisen-rearrangement-based methodology in the stereocontrolled construction of the central eight-membered ring will also be examined. The synthesis of taxinine, a member of this class of compounds, will initially be investigated and precedent the extension of this strategy to the synthesis of the antitumor agent taxol and analogs. The dibenzocyclooctadiene ring of the stegane class of compounds will also be assembled using this methodology. In particular, a synthesis of the antileukemic agent steganicin is planned. A sequential Claisen-Cope rearrangement is expected to facilitate the rapid construction of the bicyclic ring system of the very potent esperamicin and calichemic class of antitumor antibiotics. If this approach is successful, analogs will be prepared which may provide further insight into the intriguing proposed mechanism of action of this class of compounds and/or function as new chemotherapeutic agents. Finally, the cyclodecane ring system of the cockroach pheremones periplanone A and B will be assembled using an alicyclic Claisen rearrangement in projected syntheses.